Methanol → HCID 89924391, compound

HRID 1505711Notes

Reaction equation

HRID 1505711 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OC([N:26]1[CH2:31][CH2:30][CH:29]([N:32]2[CH:36]=[C:35]([C:37]3[CH:38]=[N:39][C:40]([C:43]4[CH:48]=[CH:47][CH:46]=[C:45]([C:49]5[N:50]=[N:51][N:52]([CH2:54][Si](C)(C)C)[CH:53]=5)[CH:44]=4)=[N:41][CH:42]=3)[CH:34]=[N:33]2)[CH2:28][CH2:27]1)=O)(C)(C)C.CO.[ClH:61].O1CCOCC1>C1COCC1.C([O-])(O)=O.[Na+].C(Cl)Cl>[ClH:61].[CH3:54][N:52]1[CH:53]=[C:49]([C:45]2[CH:44]=[C:43]([C:40]3[N:39]=[CH:38][C:37]([C:35]4[CH:34]=[N:33][N:32]([CH:29]5[CH2:30][CH2:31][NH:26][CH2:27][CH2:28]5)[CH:36]=4)=[CH:42][N:41]=3)[CH:48]=[CH:47][CH:46]=2)[N:50]=[N:51]1

Participants

8

Reactant 4

HCID 887MethanolHCID 2724141Tetrabutylammonium FluorideHCID 204431481,4-Dioxane hydrochlorideHCID 89924514HCID 89924514, compound

Product 1

HCID 89924391HCID 89924391, compoundYield 33%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Tetrabutylammonium fluoride (56 mg; 0.21 mmol; 2.0 eq.) was added to a solution of 4-(4-{2-[3-(1-Trimethylsilanylmethyl-1H-[1,2,3]triazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (60 mg; 0.11 mmol; 1.0 eq.) in THF (1 mL) and the reaction mixture was stirred at RT for 2 h. It was then diluted with a saturated solution of NaHCO3 and extracted with EtOAc (three times). Combined organic phases were washed with brine, dried over magnesium sulfate, filtered and concentrated. The crude obtained was dissolved in DCM (1 mL) and MeOH (MeOH) and HCl/dioxane (0.4 mL of a 4N solution, 1.6 mmol, 15 eq.) was added. The reaction mixture was stirred at RT for 2 h, concentrated under reduced pressure and purified by autopreparative LC/Ms to give the title compound as a beige solid (15 mg, 33%). 1H NMR (300 MHz, DMSO-d6) δ 9.22 (s, 2H), 9.11 (brs, 1H), 8.94-8.81 (m, 2H), 8.67 (s, 1H), 8.54 (s, 1H), 8.35 (dt, J=7.9 Hz, 1.5 Hz, 1H), 8.22 (s, 1H), 7.96 (dt, J=7.9 Hz, 1.5 Hz, 1H), 7.61 (t, J=7.9 Hz, 1H), 4.61-4.52 (m, 1H), 4.12 (s, 3H), 3.43-3.36 (m, 2H), 3.16-3.06 (m, 2H), 2.28-2.11 (m, 4H). HPLC (Condition A): Rt 2.08 min (purity 98.5%). MS (ESI+): 387.3.

Workup

  1. extractionextracted with EtOAc (three times)
  2. washCombined organic phases were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude obtained
  7. stirringThe reaction mixture was stirred at RT for 2 h
  8. concentrationconcentrated under reduced pressure
  9. custompurified by autopreparative LC/Ms

Sources & evidence

ORD record
ord-05881c8aaa3f47fa8e122bc069da8f28
Source dataset
uspto-grants-2015_12
Patent number
US09216991B2

Reaction notes

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